Figure 3. Primate SAMHD1 has been evolving under positive selection.

(A) Cladogram of 31 primate SAMHD1 genes sequenced for the evolutionary analyses. The panel of primates comprised of 8 hominoids, 16 Old World monkeys and 7 New World monkeys. No evidence of recombination was detected by a GARD analysis (Kosakovsky Pond et al., 2006). Values of ω (dN/dS) along each branch were calculated by a free ratio analysis using PAML (Figure S2B). Branches with statistically significant ω values > 1 are highlighted in red, branches highlighted in grey indicate lineages that show ω values > 1, but are not statistically significant based on two-ratio likelihood tests (Figure S2).

(B) Likelihood ratio test statistics were used to determine if SAMHD1 evolution across various primate lineages was associated with dN/dS ratios significantly greater than 1 (hence under positive selection). Neutral models (M7) were compared to selection models (M8) under the F61 model of codon substitution. Similar results were obtained in a comparison of M1 (neutral) versus M2 (selection) (data not shown). See also Figure S2.

(C) Six positively selected codons were identified (32, 36, 46, 69, 107, 486) with significant posterior probability (Figure S3A) using PAML. The analysis was performed on SAMHD1 sequences from the panel of 16 Old World monkeys, which showed the strongest burst of positive selection in primates (Figure 3B). Likelihood ratio tests were performed between the M7 (neutral) and M8 (selection) models for the full SAMHD1 gene, without the SAM domain or with amino acids 32, 36, 46, 67, 107, 486 omitted from the alignment. Domains were analyzed for signatures of positive selection, with the strongest signals located in the SAM domain. See also Figure S3.